Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, United States.
Retired, Galway, Ireland.
Front Endocrinol (Lausanne). 2022 May 12;13:860286. doi: 10.3389/fendo.2022.860286. eCollection 2022.
Vitamin D, a fat-soluble vitamin, plays a critical role in calcium homeostasis, the immune system, and normal development. Many epidemiological cohort studies globally have found high prevalence rates of vitamin D deficiency and insufficiency, recognized as an important health issue that needs to be solved. In particular, reproductive age and pregnant women low in vitamin D status may confer risks of diseases like obesity on their offspring. While observational studies have suggested associations between prenatal vitamin D deficiency and metabolic phenotypes in offspring, not yet determined is whether prenatal vitamin D deficiency permanently alters the development of the liver, a major metabolic organ. We tested the histopathology and the transcriptomic profiles of livers from male C57BL/6J mice exposed to prenatal vitamin D deficiency through a maternal dietary intervention model. We found that prenatal vitamin D deficiency increases the prevalence of histopathological changes in the liver, and alters its gene expression profile. Cell subtype proportion analysis showed that the liver of prenatal vitamin D deficiency alters non-parenchymal cells of the liver, specifically macrophages, a subset of endothelial cells, and dendritic cells. Our results indicate the long-term memory of prenatal vitamin D deficiency exposure in the adult liver, a potential contributor to offspring health risks.
维生素 D 是一种脂溶性维生素，在钙稳态、免疫系统和正常发育中起着关键作用。全球许多流行病学队列研究发现，维生素 D 缺乏和不足的患病率很高，被认为是一个需要解决的重要健康问题。特别是，处于生殖年龄和孕妇的维生素 D 水平较低，可能会使后代面临肥胖等疾病的风险。虽然观察性研究表明产前维生素 D 缺乏与后代的代谢表型之间存在关联，但尚未确定产前维生素 D 缺乏是否会永久性改变肝脏这一主要代谢器官的发育。我们通过母体饮食干预模型测试了暴露于产前维生素 D 缺乏的雄性 C57BL/6J 小鼠肝脏的组织病理学和转录组特征。我们发现，产前维生素 D 缺乏增加了肝脏组织病理学变化的发生率，并改变了其基因表达谱。细胞亚型比例分析表明，产前维生素 D 缺乏的肝脏改变了非实质细胞的肝脏，特别是巨噬细胞、内皮细胞的一个子集和树突状细胞。我们的结果表明，产前维生素 D 缺乏暴露在成年肝脏中存在长期记忆，这可能是导致后代健康风险的一个因素。
